STUDY QUESTION: Given the relevant role of the extracellular microenvironment in regulating tissue homeostasis, is testicular bacterial microbiome (BM) associated with germ cell aplasia in idiopathic non-obstructive azoospermia (iNOA)? SUMMARY ANSWER: A steady increase of dysbiosis was observed among testis with normal spermatogenesis vs. iNOA with positive sperm retrieval and iNOA with complete germ cell aplasia. WHAT IS KNOWN ALREADY: Tissue-associated BM has been reported to be a biologically important extracellular microenvironment component for numerous body habitats, but not yet for the human testis. STUDY DESIGN, SIZE, DURATION: Cross-sectional study, investigating tissue-associated BM in the testis of (i) five men with iNOA and negative sperm retrieval at microdissection testicular sperm extraction (microTESE); (ii) five men with iNOA and positive sperm retrieval at microTESE; and (iii) five normozoospermic men upon orchiectomy. Every testicular specimen was histologically classified and analyzed in terms of bacterial community. PARTICIPANTS/MATERIALS, SETTING, METHODS: Massive ultra-deep pyrosequencing was applied to investigate testis microbiome. Metagenome was analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Tissue-associated bacterial load was quantified by digital droplet PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Normozoospermic men showed small amounts of bacteria in the testis, with Actinobacteria, Bacteroidetes, Firmicutes Proteobacteria as the dominating phyla; iNOA individuals had increased amounts of bacterial DNA (P = 0.02), associated with decreased taxa richness due to the lack of Bacteroidetes and Proteobacteria (P = 2 × 10-5). Specimens with negative sperm retrieval at microTESE depicted complete germ cell aplasia and a further decrease in terms of Firmicutes and Clostridia (P < 0.05), a complete lack of Peptoniphilus asaccharolyticus, but increased amount of Actinobacteria. LIMITATIONS, REASONS FOR CAUTION: The limited number of specimens analyzed in this preliminary study deserves external validation. The paraneoplastic microenvironment could have an impact on the residential bacterial flora. WIDER IMPLICATION OF THE FINDINGS: Human testicular microenvironment is not microbiologically sterile, containing low amounts of Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. A dysbiotic bacterial community was associated with iNOA and complete germ cell aplasia. Novel findings on testicular BM could support future translational therapies of male-factor infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by URI-Urological Research Institute free funds. Authors declared no conflict of interest.
Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment / M. Alfano, R. Ferrarese, I. Locatelli, E. Ventimiglia, S. Ippolito, P. Gallina, D. Cesana, F. Canducci, L. Pagliardini, P. Viganò, M. Clementi, M. Nebuloni, F. Montorsi, A. Salonia. - In: HUMAN REPRODUCTION. - ISSN 0268-1161. - 33:7(2018 Jul), pp. 1212-1217.
|Titolo:||Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment|
|Parole Chiave:||azoospermia; male infertility; microbiome; testis; dysbiosis|
|Settore Scientifico Disciplinare:||Settore MED/24 - Urologia|
Settore MED/08 - Anatomia Patologica
|Data di pubblicazione:||lug-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/humrep/dey116|
|Appare nelle tipologie:||01 - Articolo su periodico|